Purpose

To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1.

Methods

A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants.

Results

The patient’s main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome.

Conclusion

This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

中文翻译：

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JAG1 相关视网膜病变患者的长期随访

目的

报告由JAG1 中的新突变引起的异常视网膜营养不良成人后节的长期结构和功能变化。

方法

一名 33 岁女性接受了全面的眼科检查，包括最佳矫正视力 (BCVA) 测量、散瞳眼底成像（广角眼底颜色和短波长自发荧光成像）、黄斑和周边光谱域光学相干断层扫描 (SD- OCT) 和视网膜电图 (ERG) 基线和 10 年后 43 岁。患者还接受了详细的心脏、大脑和肾脏检查的系统审查。在随访期间，使用全外显子组测序对患者及其父母进行遗传分析，以确定致病变异。

结果

患者的主诉是最近出现的双侧畏光和左眼视力模糊。检查时，最显着的视网膜发现是双侧边界清楚的前周脉络膜视网膜萎缩，从中间周边到口腔有散在的色素团块。此外，她有后极部 RPE 色素减退、视乳头周围脉络膜视网膜萎缩、左侧黄斑脉络膜皱襞和视网膜脉管系统曲折伴非典型分支。她的视网膜电生理学符合锥杆光感受器营养不良和左侧黄斑功能障碍。十年后，她的BCVA、前周脉络膜视网膜萎缩和视野收缩都保持稳定。她的视网膜电生理显示左视杆功能恶化，而视锥功能障碍保持稳定。双眼黄斑功能恶化。在随访期间，她还被发现有进行性主动脉根部扩张、后部胚胎毒素和蝴蝶椎骨的 X 射线诊断。全外显子组测序揭示了一个新的 c.2412C > A p.(Tyr804Ter) 截断突变JAG1被预测为致病性并提示诊断为 Alagille 综合征。

结论

这是对 Alagille 综合征患者进行长期详细随访的第一份报告，该患者最引人注目的眼科发现是双侧边界清楚的前周脉络膜视网膜萎缩。在随访期间，这一发现保持稳定，表明这可能是发育性的。这与后极部视网膜和黄斑功能的逐渐恶化形成对比。